The vast regulatory potential of the adenylate energy system (adenylate kinase, ATP) ADP, and AMP) allows for interpretation for possible regulation of multiple metabolic pathways, some of which are essential for maintenance of the differentiated state. We have observed serveral alterations in the regulatory capacity of this system in hepatomas. These alterations could have serious effects upon the tumor tissue's ability to maintain a homeostatic internal environment under changing external conditions. We propose to examine the adenylate energy charge system in normal and neoplastic tissues in regard to modulation by intracellular metabolites (citric acid cycle intermediates and other purine nucleotides), free fatty acid esters, divalent metals, and the various classes of prostaglandins. Alterations in metabolic controls of this kind could be an essential requirement for malignancy.